A serum glycomics approach to breast cancer biomarkers

Crystal Kirmiz, Bensheng Li, Hyun Joo An, Brian H. Clowers, Helen K Chew, Kit Lam, Anthony Ferrige, Robert Alecio, Alexander D Borowsky, Shola Sulaimon, Carlito B Lebrilla, Suzanne Miyamoto

Research output: Contribution to journalArticle

178 Citations (Scopus)

Abstract

Because the glycosylation of proteins is known to change in tumor cells during the development of breast cancer, a glycomics; approach is used here to find relevant biomarkers of breast cancer. These glycosylation changes are known to correlate with increasing tumor burden and poor prognosis. Current antibody-based immunochemical tests for cancer biomarkers of ovarian (CA125), breast (CA27.29 or CA15-3), pancreatic, gastric, colonic, and carcinoma (CA19-9) target highly glycosylated mucin proteins. However, these tests lack the specificity and sensitivity for use in early detection. This glycomics approach to find glycan biomarkers of breast cancer involves chemically cleaving oligosaccharides (glycans) from glycosyated proteins that are shed or secreted by breast cancer tumor cell lines. The resulting free glycan species are analyzed by MALDI-FT-ICR MS. Further structural analysis of the glycans can be performed in FTMS through the use of tandem mass spectrometry with infrared multiphoton dissociation. Glycan profiles were generated for each cell line and compared. These methods were then used to analyze sera obtained from a mouse model of breast cancer and a small number of serum samples obtained from human patients diagnosed with breast cancer or patients with no known history of breast cancer. In addition to the glycosylation changes detected in mice as mouse mammary tumors developed, glycosylation profiles were found to be sufficiently different to distinguish patients with cancer from those without. Although the small number of patient samples analyzed so far is inadequate to make any legitimate claims at this time, these promising but very preliminary results suggest that glycan profiles may contain distinct glycan biomarkers that may correspond to glycan "signatures of cancer."

Original languageEnglish (US)
Pages (from-to)43-55
Number of pages13
JournalMolecular and Cellular Proteomics
Volume6
Issue number1
DOIs
StatePublished - Jan 2007

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Glycomics
Tumor Biomarkers
Polysaccharides
Breast Neoplasms
Glycosylation
Serum
Tumors
Biomarkers
Cells
Proteins
Neoplasms
Mucins
Oligosaccharides
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Structural analysis
Tandem Mass Spectrometry
Tumor Burden
Tumor Cell Line
Mass spectrometry
Stomach

ASJC Scopus subject areas

  • Biochemistry

Cite this

A serum glycomics approach to breast cancer biomarkers. / Kirmiz, Crystal; Li, Bensheng; An, Hyun Joo; Clowers, Brian H.; Chew, Helen K; Lam, Kit; Ferrige, Anthony; Alecio, Robert; Borowsky, Alexander D; Sulaimon, Shola; Lebrilla, Carlito B; Miyamoto, Suzanne.

In: Molecular and Cellular Proteomics, Vol. 6, No. 1, 01.2007, p. 43-55.

Research output: Contribution to journalArticle

Kirmiz, C, Li, B, An, HJ, Clowers, BH, Chew, HK, Lam, K, Ferrige, A, Alecio, R, Borowsky, AD, Sulaimon, S, Lebrilla, CB & Miyamoto, S 2007, 'A serum glycomics approach to breast cancer biomarkers', Molecular and Cellular Proteomics, vol. 6, no. 1, pp. 43-55. https://doi.org/10.1074/mcp.M600171-MCP200
Kirmiz, Crystal ; Li, Bensheng ; An, Hyun Joo ; Clowers, Brian H. ; Chew, Helen K ; Lam, Kit ; Ferrige, Anthony ; Alecio, Robert ; Borowsky, Alexander D ; Sulaimon, Shola ; Lebrilla, Carlito B ; Miyamoto, Suzanne. / A serum glycomics approach to breast cancer biomarkers. In: Molecular and Cellular Proteomics. 2007 ; Vol. 6, No. 1. pp. 43-55.
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